Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions

Telomere shortening is the mechanism underlying replicative aging in fibrob lasts. A variety of reports now claim that inactivation of the p16(INK4a)/p RB pathway is required in addition to telomere maintenance for the immortal ization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be expl ained by an inadequate culture environment. Providing mesenchymal/epithelia l interactions by cultivating the telomerase-expressing cells on feeder lay ers avoids the growth arrest associated with increased p16(INK4a). These re sults do not support a telomere-independent mechanism of replicative aging.